We propose to examine the relation of chronic lead (Pb) exposure to adverse pregnancy outcome and infant development. The study draws upon a unique community surrounding a Pb smelter in Titova Mitrovica, Yugoslavia. Subjects will also be studied in Pristina, a non-Pb-exposed town 25 miles to the south. Almost no other locations in the world can provide such a wide range of Pb exposures. Work in progress examines the effects of prenatal Pb exposure on pregnancy outcome in approximately 790 women in Mitrovica and 1190 in Pristina. Preliminary data from a total of 590 pregnant women, examined at 12-20 weeks of gestation, indicate that blood lead (BPb) concentrations in Mitrovica range from 2-42 Mug/dl, with a mean of 16.3 Mug/dl; in Pristina, the mean BPb is 5.7 Mug/dl. Questionnaire data reassure us that our populations are comparable with regard to maternal and paternal age and education, maternal height and weight, number of previous pregnancies, ethnicity and measures of socioeconomic status. We will determine whether exposure to Pb is associated with an increased risk of selected adverse pregnancy outcomes: late spontaneous abortion and stillbirth, premature delivery, intrauterine growth retardation and congenital malformations. Preliminary data concerning past pregnancies in these subjects suggests that Pb exposure may be associated with increased risk for spontaneous abortion. Thus far, blood specimens from women enrolled in the study reveal a strong correlation between BPb at midpregnancy and at term. Likewise, there is a strong relation between maternal BPb at term and umbilical cord BPb. In Mitrovica, mean cord BPb is 16.2 Mug/dl. We propose to assess infant development in relation to pre- and postnatal Pb exposure. In Mitrovica, we will follow during the first 2 years of life 3 subsets of infants born to women in the pregnancy study: a) the 144 infants with the highest cord BPb's; b) 120 infants with the lowest BPb's; and c) a random sample of 120 infants from the remaining births. Two matched control groups of infants in Pristina will also be followed. The infants will be evaluated for BPb and measures of physical, behavioral, and cognitive-linguistic development at 6, 12, 18 and 24 months. We will also examine Pb mobilization in all infants found to have a BPb greater than 24 Mug/dl at any time during the study; those with positive CaNa2EDTA challenge tests will be chelated according to current US guidelines. In young infants, little is known about the size of the chelatable Pb pool, thought to be metabolically toxic.